1.Outcomes of Early Versus Later Anticoagulation in Asian Atrial Fibrillation–Related Stroke: ELAN Subgroup Analysis
Takeshi YOSHIMOTO ; Masafumi IHARA ; P N SYLAJA ; Jean-Benoît ROSSEL ; Shigeru FUJIMOTO ; Yasuyuki IGUCHI ; Rajsrinivas PARTHASARTHY ; Vijaya PAMIDIMUKKALA ; Yusuke YAKUSHIJI ; Thomas IYPE ; Makoto NAKAJIMA ; Dheeraj KHURANA ; Vivek NAMBIAR ; Hisanao AKIYAMA ; Kazunori TOYODA ; Angelika ALONSO ; Sven POLI ; Caterina KULYK ; Nicoletta G. CARACCIOLO ; Dimitri HEMELSOET ; Ana Paiva NUNES ; Jeyaraj Durai PANDIAN ; Jesse DAWSON ; Urs FISCHER ; Masatoshi KOGA
Journal of Stroke 2026;28(2):293-302
Background:
and Purpose We aimed to evaluate whether early versus late initiation of direct oral anticoagulant (DOAC) after acute ischemic stroke (AIS) yields different safety and efficacy outcomes in Asian versus non-Asian patients.
Methods:
We analyzed Early versus Late initiation of direct oral Anticoagulants in post-ischaemic stroke patients with atrial fibrillatioN (ELAN) trial data from 2,013 AIS patients with atrial fibrillation (AF) randomized to early (≤48 hours for minor/moderate stroke, 6–7 days for major stroke) or late DOAC initiation (3–4 days for minor ischemic stroke, 6–7 days for moderate ischemic stroke, 12–14 days for major ischemic stroke). Patients were categorized by region as Asian (Japan and India) or non-Asian. The primary outcome was a composite of major extracranial bleeding, symptomatic uncerintracranial hemorrhage (SICH), recurrent ischemic stroke, systemic embolism (SE), or vascular death at 30 days (trial registration: ClinicalTrials.gov number, NCT03148457).
Results:
Among 1,975 patients, 245 were Asian (192 from Japan and 53 from India) and 1,730 were non-Asian. The primary outcome occurred in 6.5% of Asian patients (4.8% early vs. 8.3% late) and 3.1% of non-Asian patients (2.7% vs. 3.6%) (p<0.01). Higher rates of recurrent ischemic stroke (4.1% [2.4% vs. 5.8%] vs. 1.7% [1.3% vs. 2.1%], p=0.02) and SE (2.0% [0.8% vs. 3.3%] vs. 0.5% [0.4% vs. 0.6%], p=0.02) accounted for this difference. No significant differences were observed in major extracranial bleeding, SICH, recurrent ischemic stroke, SE, or vascular death. No significant interaction was observed between region and treatment allocation.
Conclusions
Although Asian patients had worse baseline profiles and outcomes, treatment effects did not differ by region, supporting the generalizability of early DOAC initiation in Asian AIS patients without region-specific timing modifications.
2.Antiplatelet Use Prior to Anticoagulant Initiation in Patients With Atrial Fibrillation-Related Ischemic Stroke: An ELAN Trial Analysis
Alexandros A. POLYMERIS ; Masatoshi KOGA ; Daniel STRBIAN ; Adhiyaman VEDAMURTHY ; Manju KRISHNAN ; Mattia BRANCA ; Thomas HORVATH ; Martina GOELDLIN ; Gek SHIM ; Christoph GUMBINGER ; Liqun ZHANG ; Espen Saxhaug KRISTOFFERSEN ; Philippe DESFONTAINES ; Peter VANACKER ; Angelika ALONSO ; Sven POLI ; Ana Paiva NUNES ; Nicoletta G. CARACCIOLO ; Markus KNEIHSL ; Timo KAHLES ; Daria GIUDICI ; Silja RÄTY ; Marjaana TIAINEN ; Jesse DAWSON ; Urs FISCHER ;
Journal of Stroke 2025;27(2):217-227
Background:
and Purpose Antiplatelets are often used before direct oral anticoagulant (DOACs) initiation after an acute ischemic stroke related to atrial fibrillation (AF), but the evidence is weak. Here, we explored the risks and benefits of this approach.
Methods:
A post-hoc analysis of ELAN (Early versus Late Initiation of Direct Oral Anticoagulants in Post-ischemic Stroke Patients with Atrial Fibrillation) trial data (NCT03148457) was conducted to compare the risk of recurrent ischemic stroke, systemic embolism, major bleeding (extracranial or intracranial hemorrhage [ICH]), and vascular death within 30 days (as a composite and as individual outcomes) in participants treated with and without antiplatelets before DOAC initiation after an AF-associated ischemic stroke. We used both logistic and cause-specific Cox proportional hazards regression in inverse probability of treatment weighted models to account for confounding. We calculated the net benefit of antiplatelet use by subtracting the weighted rate of excess bleeding events attributable to antiplatelets from the rate of excess ischemic events possibly prevented by antiplatelets.
Results:
Among 2,013 participants (median age 77 years, 45.5% female), 1,090 (54.1%) used antiplatelets, and 70 (3.5%) experienced the composite outcome. Antiplatelet use was not associated with the composite outcome (inverse probability of treatment weighted odds ratio [ORweighted] 1.06, 95% confidence interval [CI] 0.66–1.72; inverse probability of treatment weighted hazard ratio [HRweighted] 1.06, 95% CI 0.65–1.72), but showed a lower risk of ischemic stroke recurrence (ORweighted 0.58 [0.30–1.08], HRweighted 0.57 [0.30–1.10]), and a higher risk of major bleeding (ORweighted 1.76 [0.56–6.63], HRweighted 1.88 [0.56–6.39]). Its net benefit was +0.57 (95% CI -1.25 to +2.34) to +0.30 (-1.82 to +2.27) weighted events/100 person-months for ICH weights 1.5 to 3.1.
Conclusion
Following an AF-associated ischemic stroke, we found a lower risk of recurrence and no signs of net harm with antiplatelet use before DOAC initiation, despite an increased risk of bleeding.
3.Antiplatelet Use Prior to Anticoagulant Initiation in Patients With Atrial Fibrillation-Related Ischemic Stroke: An ELAN Trial Analysis
Alexandros A. POLYMERIS ; Masatoshi KOGA ; Daniel STRBIAN ; Adhiyaman VEDAMURTHY ; Manju KRISHNAN ; Mattia BRANCA ; Thomas HORVATH ; Martina GOELDLIN ; Gek SHIM ; Christoph GUMBINGER ; Liqun ZHANG ; Espen Saxhaug KRISTOFFERSEN ; Philippe DESFONTAINES ; Peter VANACKER ; Angelika ALONSO ; Sven POLI ; Ana Paiva NUNES ; Nicoletta G. CARACCIOLO ; Markus KNEIHSL ; Timo KAHLES ; Daria GIUDICI ; Silja RÄTY ; Marjaana TIAINEN ; Jesse DAWSON ; Urs FISCHER ;
Journal of Stroke 2025;27(2):217-227
Background:
and Purpose Antiplatelets are often used before direct oral anticoagulant (DOACs) initiation after an acute ischemic stroke related to atrial fibrillation (AF), but the evidence is weak. Here, we explored the risks and benefits of this approach.
Methods:
A post-hoc analysis of ELAN (Early versus Late Initiation of Direct Oral Anticoagulants in Post-ischemic Stroke Patients with Atrial Fibrillation) trial data (NCT03148457) was conducted to compare the risk of recurrent ischemic stroke, systemic embolism, major bleeding (extracranial or intracranial hemorrhage [ICH]), and vascular death within 30 days (as a composite and as individual outcomes) in participants treated with and without antiplatelets before DOAC initiation after an AF-associated ischemic stroke. We used both logistic and cause-specific Cox proportional hazards regression in inverse probability of treatment weighted models to account for confounding. We calculated the net benefit of antiplatelet use by subtracting the weighted rate of excess bleeding events attributable to antiplatelets from the rate of excess ischemic events possibly prevented by antiplatelets.
Results:
Among 2,013 participants (median age 77 years, 45.5% female), 1,090 (54.1%) used antiplatelets, and 70 (3.5%) experienced the composite outcome. Antiplatelet use was not associated with the composite outcome (inverse probability of treatment weighted odds ratio [ORweighted] 1.06, 95% confidence interval [CI] 0.66–1.72; inverse probability of treatment weighted hazard ratio [HRweighted] 1.06, 95% CI 0.65–1.72), but showed a lower risk of ischemic stroke recurrence (ORweighted 0.58 [0.30–1.08], HRweighted 0.57 [0.30–1.10]), and a higher risk of major bleeding (ORweighted 1.76 [0.56–6.63], HRweighted 1.88 [0.56–6.39]). Its net benefit was +0.57 (95% CI -1.25 to +2.34) to +0.30 (-1.82 to +2.27) weighted events/100 person-months for ICH weights 1.5 to 3.1.
Conclusion
Following an AF-associated ischemic stroke, we found a lower risk of recurrence and no signs of net harm with antiplatelet use before DOAC initiation, despite an increased risk of bleeding.
4.Antiplatelet Use Prior to Anticoagulant Initiation in Patients With Atrial Fibrillation-Related Ischemic Stroke: An ELAN Trial Analysis
Alexandros A. POLYMERIS ; Masatoshi KOGA ; Daniel STRBIAN ; Adhiyaman VEDAMURTHY ; Manju KRISHNAN ; Mattia BRANCA ; Thomas HORVATH ; Martina GOELDLIN ; Gek SHIM ; Christoph GUMBINGER ; Liqun ZHANG ; Espen Saxhaug KRISTOFFERSEN ; Philippe DESFONTAINES ; Peter VANACKER ; Angelika ALONSO ; Sven POLI ; Ana Paiva NUNES ; Nicoletta G. CARACCIOLO ; Markus KNEIHSL ; Timo KAHLES ; Daria GIUDICI ; Silja RÄTY ; Marjaana TIAINEN ; Jesse DAWSON ; Urs FISCHER ;
Journal of Stroke 2025;27(2):217-227
Background:
and Purpose Antiplatelets are often used before direct oral anticoagulant (DOACs) initiation after an acute ischemic stroke related to atrial fibrillation (AF), but the evidence is weak. Here, we explored the risks and benefits of this approach.
Methods:
A post-hoc analysis of ELAN (Early versus Late Initiation of Direct Oral Anticoagulants in Post-ischemic Stroke Patients with Atrial Fibrillation) trial data (NCT03148457) was conducted to compare the risk of recurrent ischemic stroke, systemic embolism, major bleeding (extracranial or intracranial hemorrhage [ICH]), and vascular death within 30 days (as a composite and as individual outcomes) in participants treated with and without antiplatelets before DOAC initiation after an AF-associated ischemic stroke. We used both logistic and cause-specific Cox proportional hazards regression in inverse probability of treatment weighted models to account for confounding. We calculated the net benefit of antiplatelet use by subtracting the weighted rate of excess bleeding events attributable to antiplatelets from the rate of excess ischemic events possibly prevented by antiplatelets.
Results:
Among 2,013 participants (median age 77 years, 45.5% female), 1,090 (54.1%) used antiplatelets, and 70 (3.5%) experienced the composite outcome. Antiplatelet use was not associated with the composite outcome (inverse probability of treatment weighted odds ratio [ORweighted] 1.06, 95% confidence interval [CI] 0.66–1.72; inverse probability of treatment weighted hazard ratio [HRweighted] 1.06, 95% CI 0.65–1.72), but showed a lower risk of ischemic stroke recurrence (ORweighted 0.58 [0.30–1.08], HRweighted 0.57 [0.30–1.10]), and a higher risk of major bleeding (ORweighted 1.76 [0.56–6.63], HRweighted 1.88 [0.56–6.39]). Its net benefit was +0.57 (95% CI -1.25 to +2.34) to +0.30 (-1.82 to +2.27) weighted events/100 person-months for ICH weights 1.5 to 3.1.
Conclusion
Following an AF-associated ischemic stroke, we found a lower risk of recurrence and no signs of net harm with antiplatelet use before DOAC initiation, despite an increased risk of bleeding.
5.Fulminant Cytotoxic Edema in a Patient with Pneumococcal Meningoencephalitis
Angelika ALONSO ; Nima ETMINAN ; Joerg KREBS ; Kristina SZABO ; Michael PLATTEN ; Alex FÖRSTER
Journal of Clinical Neurology 2019;15(4):575-577
No abstract available.
Edema
;
Humans
;
Meningoencephalitis

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